BACKGROUND: Mycoplasma pneumoniae (MP) is a major cause of community-acquired pneumonia (CAP), posing diagnostic challenges. This study evaluates novel inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII) and system inflammation response index (SIRI) for MP diagnosis in children. METHODS: Complete blood count (CBC) results of 424 children with MP infection and 150 health children were collected. NLR, MLR, PLR, SII and SIRI, were respectively calculated. Shapiro-Wilk test, Student's t-test, Mann-Whitney U-test and Pearson chi-squared test were used to analyze the clinical data of the patients and participants. Multiple logistic regression analysis was conducted based on the results of single factor analysis. Receiver operating characteristic (ROC) curve was drawn to evaluate the potential of the above biomarkers for MP infection. RESULTS: Compared with the control group, white blood cell (WBC) count, neutrophil (NEU) count, monocyte (MON) count, NLR, MLR, PLR, SII and SIRI were significantly higher and lymphocyte count (LYM) and platelet (PLT) were significantly lower than those in MP group. The results of multivariate logistic regression analysis indicate that MLR and SIRI can serve as major risk factors for MP infection in children. The predictive accuracy of logistic regression model based on MLR and SIRI is 83.28%. The area under the curve (AUC) results showed that SIRI has better predicting value of MP infection (AUC = 0.892, Sensitivity = 75.7%, Specificity = 92.0%). CONCLUSION: This study described the significance of novel inflammatory biomarkers in children with MP infection and may provide new auxiliary diagnostic indicators for MP infection.